Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/7095
Title: Sulforaphane prevents diabetes-induced hepatic ferroptosis by activating Nrf2 signaling axis
Authors: Savic, Nevena
Markelić, Milica 
Stancic, Ana
Veličković, Ksenija 
Grigorov, Ilijana
Vucetic, Milica
Martinovic, Vesna
Gudelj, Andjelija
Otasevic, Vesna
Keywords: GSH metabolism;Nrf2;diabetes;ferritinophagy;ferroptosis;iron metabolism;liver pathology;sulforaphane
Issue Date: 1-Feb-2024
Rank: M21
Publisher: IUBMB Journals
Project: The Ministry of Science, Technological Development and Innovation of the Republic of Serbia
Science Fund of the Republic of Serbia (Serbian Science andDiaspora Collaboration Program: Knowledge ExchangeVouchers, Ferroptosis in the b-cells death: possible strategy for diabetes treatment, acronym:BetFeSis)
Journal: BioFactors (Oxford, England)
Abstract: 
Recently, we characterized the ferroptotic phenotype in the liver of diabetic mice and revealed nuclear factor (erythroid-derived-2)-related factor 2 (Nrf2) inactivation as an integral part of hepatic injury. Here, we aim to investigate whether sulforaphane, an Nrf2 activator and antioxidant, prevents diabetes-induced hepatic ferroptosis and the mechanisms involved. Male C57BL/6 mice were divided into four groups: control (vehicle-treated), diabetic (streptozotocin-induced; 40 mg/kg, from Days 1 to 5), diabetic sulforaphane-treated (2.5 mg/kg from Days 1 to 42) and non-diabetic sulforaphane-treated group (2.5 mg/kg from Days 1 to 42). Results showed that diabetes-induced inactivation of Nrf2 and decreased expression of its downstream antiferroptotic molecules critical for antioxidative defense (catalase, superoxide dismutases, thioredoxin reductase), iron metabolism (ferritin heavy chain (FTH1), ferroportin 1), glutathione (GSH) synthesis (cystine-glutamate antiporter system, cystathionase, glutamate-cysteine ligase catalitic subunit, glutamate-cysteine ligase modifier subunit, glutathione synthetase), and GSH recycling - glutathione reductase (GR) were reversed/increased by sulforaphane treatment. In addition, we found that the ferroptotic phenotype in diabetic liver is associated with increased ferritinophagy and decreased FTH1 immunopositivity. The antiferroptotic effect of sulforaphane was further evidenced through the increased level of GSH, decreased accumulation of labile iron and lipid peroxides (4-hydroxy-2-nonenal, lipofuscin), decreased ferritinophagy and liver damage (decreased fibrosis, alanine aminotransferase, and aspartate aminotransferase). Finally, diabetes-induced increase in serum glucose and triglyceride level was significantly reduced by sulforaphane. Regardless of the fact that this study is limited by the use of one model of experimentally induced diabetes, the results obtained demonstrate for the first time that sulforaphane prevents diabetes-induced hepatic ferroptosis in vivo through the activation of Nrf2 signaling pathways. This nominates sulforaphane as a promising phytopharmaceutical for the prevention/alleviation of ferroptosis in diabetes-related pathologies.
URI: https://biore.bio.bg.ac.rs/handle/123456789/7095
ISSN: 0951-6433
1872-8081
DOI: 10.1002/biof.2042
Appears in Collections:Journal Article

Show full item record

SCOPUSTM   
Citations

3
checked on Nov 1, 2024

Page view(s)

3
checked on Nov 4, 2024

Google ScholarTM

Check

Altmetric

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.